Current opinions in immune checkpoint inhibitors rechallenge in solid cancers

Gobbini, Elisa; Charles, J.; Toffart, Anne Claire; Leccia, Marie Thérèse; Moro-Sibilot, Denis; Levra, Matteo Giaj

doi:10.1016/j.critrevonc.2019.102816

Cited by 22 publications

(15 citation statements)

References 29 publications

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“…Since the identification of nitrogen mustard as an anti-cancer drug in 1940s, pharmaceutical options for malignant disease have remarkably progressed to increasingly targeted therapies [ 1 ]. Cancer immunotherapy using immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (PD-1) drugs or anti-cytotoxic T lymphocytes-associated protein 4 (CTLA-4) drugs have become common in the clinical setting [ 2 ]. ICIs harness the human immune system to attack tumors, predominantly by enhancing the anti-tumor activity of cytotoxic T lymphocytes (i.e., effector T cells, Teffs) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The Roles of TNFR2 Signaling in Cancer Cells and the Tumor Microenvironment and the Potency of TNFR2 Targeted Therapy

Takahashi

Yoshimatsu

Faustman

2022

Cells

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The appreciation that cancer growth is promoted by a dynamic tumor microenvironment (TME) has spawned novel approaches to cancer treatment. New therapies include agents that activate quiescent T effector cells and agents that interfere with abnormal neovascularity. Although promising, many experimental therapies targeted at the TME have systemic toxicity. Another approach is to target the TME with greater specificity by taking aim at the tumor necrosis factor receptor 2 (TNFR2) signaling pathway. TNFR2 is an attractive molecular target because it is rarely expressed in normal tissues (thus, has low potential for systemic toxicity) and because it is overexpressed on many types of cancer cells as well as on associated TME components, such as T regulatory cells (Tregs), tumor-associated macrophages, and other cells that facilitate tumor progression and spread. Novel therapies that block TNFR2 signaling show promise in cell culture studies, animal models, and human studies. Novel antibodies have been developed that expressly kill only rapidly proliferating cells expressing newly synthesized TNFR2 protein. This review traces the origins of our understanding of TNFR2’s multifaceted roles in the TME and discusses the therapeutic potential of agents designed to block TNFR2 as the cornerstone of a TME-specific strategy.

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Section: Introductionmentioning

confidence: 99%

The Roles of TNFR2 Signaling in Cancer Cells and the Tumor Microenvironment and the Potency of TNFR2 Targeted Therapy

Takahashi

Yoshimatsu

Faustman

2022

Cells

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“…In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death-1 (PD-1) receptor or ligand (PD-L1) inhibitors, have changed the treatment approach for various cancers (6,7). ICIs may be effective in GC because of a relatively high mutational load (8), and clinical trials with pembrolizumab or nivolumab showed a wide range of response (10-26%) in mGC in the salvage setting (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Blood alkaline phosphatase predicts prognosis of patients with advanced HER2-negative gastric cancer receiving immunotherapy

Hu¹,

Yang²,

Wang³

et al. 2021

Ann Transl Med

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Background: Immune checkpoint blockade is effective against many cancer types, but few patients achieve a complete response (OR). Therefore, effective prognostic biomarkers are needed for metastatic gastric cancer (GC) patients after immune treatment. The present study assessed the value of hematological parameters as markers of the effectiveness of immune checkpoint blockade among metastatic GC patients.Methods: This retrospective study included patients with metastatic GC who underwent multiline chemotherapy including at least two courses of immunotherapy between September 2018 and December 2020. Patient and tumor characteristics were tested for prognostic significance by analysis of variance or chisquare test. Kaplan-Meier and Cox analyses were performed to identify factors associated with progressionfree survival (PFS).Results: Sixty-one GC patients (mean age 55.61±11.97 years, range 23-80 years, 24 females, and 37 males) were included, and 27, 9 and 25 cases had organ only, peritoneum only, and simultaneous organ and peritoneum metastasis, respectively. Gastrectomy was performed in 24 cases, and there was no operative treatment in the other 37 cases, while all patients received two or more lines of chemotherapy. After immune treatment, 13 patients achieved a partial response (PR), 16 stable disease (SD), and 32 progressive disease (PD). The median PFS was 4.93±3.47 months. An alkaline phosphatase (ALP) level >225 U/L, a lactate dehydrogenase level (LDH) >299 U/L, and a body mass index (BMI) >24 kg/m 2 were associated with a short PFS (P=0.01, P=0.008, and P=0.039, respectively). A Cox multivariate proportional hazard model indicated that higher ALP level was a significant prognostic indicator for adverse PFS.Conclusions: Our data show an ALP cutoff of 225 U/L offered good prognostic sensitivity for HER2negative metastatic GC. ALP measurement represents a convenient, cost-effective, and relatively sensitive screening tool, and prospective studies involving its evaluation in addition to other biomarkers in metastatic GC patients are indicated.

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“…163 Indeed, for some oncotherapeutics (eg, ICI for solid cancers), rechallenge after TAEAT is increasingly being accepted. 40,71,[164][165][166][167][168][169][170] The decision to resume treatment after the detection of hepatitis/ hepatotoxicity is based on individualized risk:benefit assessments, 40,[167][168][169][170] and these considerations should likely apply to rechallenge after the confirmation of elevated aminotransferase levels. Although current recommendations for rechallenge are outlined in the approved prescribing information (Table 1), further discussion is needed with a goal to generate patient-tailored decision-making algorithms to ensure optimal patient outcomes.…”

Section: Should Taeat Management Include Drug Interruption and Rechal...mentioning

confidence: 99%

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology

Lewis

Khaldoyanidi

Britten

et al. 2022

American Journal of Clinical Oncology

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Monitoring for liver injury remains an important aspect of drug safety assessment, including for oncotherapeutics. When present, drug-induced liver injury may limit the use or result in the discontinuation of these agents. Drug-induced liver injury can exhibit with a wide spectrum of clinical and biochemical manifestations, ranging from transient asymptomatic elevations in aminotransferases (TAEAT) to acute liver failure. Numerous oncotherapeutics have been associated with TAEAT, with published reports indicating a phenomenon in which patients may be asymptomatic without overt liver injury despite the presence of grade ≥3 aminotransferase elevations. In this review, we discuss the occurrence of TAEAT in the context of oncology clinical trials and clinical practice, as well as the clinical relevance of this phenomenon as an adverse event in response to oncotherapeutics and the related cellular and molecular mechanisms that may underlie its occurrence. We also identify several gaps in knowledge relevant to the diagnosis and the management of TAEAT in patients receiving oncotherapeutics, and identify areas warranting further study to enable the future development of consensus guidelines to support clinical decision-making.

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Current opinions in immune checkpoint inhibitors rechallenge in solid cancers

Cited by 22 publications

References 29 publications

The Roles of TNFR2 Signaling in Cancer Cells and the Tumor Microenvironment and the Potency of TNFR2 Targeted Therapy

The Roles of TNFR2 Signaling in Cancer Cells and the Tumor Microenvironment and the Potency of TNFR2 Targeted Therapy

Blood alkaline phosphatase predicts prognosis of patients with advanced HER2-negative gastric cancer receiving immunotherapy

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology

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